This proposal is designed to document the ability of islet transplantation to prevent or reverse the secondary complications of experimental diabetes by providing normal metabolic homeostasis. Age-matched normal and diabetic rats will be used as controls. Portal vein islet transplantation will be performed both acutely following stabilization of diabetes and after six months of diabetes to determine the effect of the duration of diabetes on altering the complications. Transplantation will be performed using differing amounts of isolated islets to be able to precisely control the degree of insulin release. This will permit us to define the ability of reduced insulin responsiveness to lead to the development of microangiopathy. All animals in the study will have daily urine volumes, bi-weekly urine glucose, fasting serum glucose, fasting serum glucose and body weights in addition to intravenous and oral glucose tolerance testing at regular intervals. This data will permit us to correlate hyperglycemia and insulin responsiveness with measured ocular fluorophotometry and serum glycosylated hemoglobins and haptoglobins along with pathologic changes in the eye, kidney and nerves of control, diabetic and transplant recipients. We should thus be able to not only learn more about the pathogenesis of the diabetic complications but also understand the effectiveness of islet transplantation in preventing or reversing these complications.